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Role of NO and the NADPH Oxidase in Hyperhomocysteinemia induced Cardiac Metabolic Dysfunction in Pregnancy
Author(s) -
Song Su,
Huang Harer,
MartinFernandez Beatriz,
Ojaimi Caroline,
Kaminski Pavel,
Zhang Suhua,
Wang Ziping,
Wolin Michael,
Hintze Thomas
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.984.7
Subject(s) - nadph oxidase , medicine , endocrinology , hyperhomocysteinemia , nitrotyrosine , apocynin , chemistry , homocysteine , oxidative stress , nitric oxide , nitric oxide synthase
Hyperhomocysteinemia (HHcy) causes cardiovascular dysfunction and is associated with many complications during pregnancy related to reduced NO bioactivity. This study assessed the mechanisms of HHcy on the NO‐dependent control of cardiac O2 consumption in pregnant rats. Rats were mated 3 times and were fed Met in drinking water to increase plasma Hcy (3.0±1.2 to 14.6±8.9 uM at the end of 1st pregnancy). This caused significant increase of heart wt/body wt (0.24±0.01 to 0.27±0.01 g/100g) and LV wt (0.69±0.03 to 0.78±0.01 g). The ability of bradykinin and carbachol to reduce myocardial O2 consumption in vitro was impaired by 59% and 66% in heart. The response was restored by ascorbic acid, tempol or apocynin. O2− production was increased by 2.5 folds in Hcy heart using lucigenin chemiluminescence. After the 1st pregnancy, HHcy caused a 51% increase in the p47phox subunit of NADPH oxidase, an increase in Rac‐1(67%) and increased nitrotyrosine (21%). Microarray analysis from heart tissues revealed 853 genes to be differentially regulated (P<0.05). There were no changes in the NADPH oxidase subunits or NOS. However, there were up regulation of some structural genes (Myosin, MMP3) and metabolic genes (Aldehyde DH, pyruvate DH and NADH DH). HHcy increases O2− production by NADPH oxidase and reduces the ability of NO to regulate myocardial O2 consumption in pregnancy. Supported by PO‐43023, HL 50142